Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction
- Belinostat is an experimental cancer treatment drug that works by helping to turn on genes that limit cell growth and survival of the tumor that are switched off in cancer cells. Belinostat has been given to patients with different types of cancer to measure its safety and effectiveness, but it has not been given in a formal trial to cancer patients who have abnormal liver function. Because belinostat is processed by the liver, its safety and effectiveness needs to be established in individuals who have abnormal liver function. Researchers are interested in comparing the effects of belinostat as a cancer treatment drug in individuals with normal and abnormal liver function.
- To test the safety and effectiveness of belinostat in individuals who have solid tumors and lymphomas and who also have abnormal liver function.
- To compare the results of belinostat treatment in individuals with normal and abnormal liver function.
- Individuals at least 18 years of age who have been diagnosed with solid tumors or lymphomas that have not responded to standard treatment.
- Individuals with normal liver function and varying degrees of abnormal liver function (mild, moderate, severe) are eligible.
- Participants will be screened with a full medical history and physical examination, as well as blood and urine tests, and tumor imaging studies. Participants will then be divided into study groups based on their liver function.
- Participants will receive belinostat in cycles of treatment. Except for cycle 1, all cycles will last 21 days. Cycle 1 will last 28 days. For cycle 1 only, participants will receive a single dose of belinostat 1 week before the regular 21-day treatment cycle starts.
- In each cycle, participants will receive belinostat once a day for 5 days, and will be asked to keep a medication diary to record any side effects.
- Participants will have regular clinic visits with blood and urine samples and imaging studies to evaluate the cancer s response to treatment.
- Participants may continue to take belinostat for as long as the cancer responds to the treatment....
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Pharmacokinetic Study of Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction|
- Safety and tolerability [ Time Frame: Cycle 1 ] [ Designated as safety issue: Yes ]
- Evaluate the pharmacokinetics of one dose of belinostat (400 mg/m2) in patients with varying degrees of liver dysfunction [ Time Frame: Study day 7 ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Four cohorts: normal, mild, moderate, and severe hepatic dysfunction
Patients divided into 4 cohorts based on level of liver dysfunction. Belinostat administered IV over 30 minutes. On day -7 (Cycle 1 only), all patients receive a single dose of 400 mg/m2 belinostat. On days 1 5 of each cycle, patients receive belinostat at a dose dependent on the level of hepatic dysfunction (125-1000 mg/m2/day)
- Belinostat is a histone deacetylase (HDAC) inhibitor. HDACs are frequently deregulated in cancer cells, leading to an increase in deacetylation and the silencing of genes that normally control cell cycle arrest and apoptosis.
- Belinostat has growth inhibitory activity in several malignancies in vitro and in vivo, both as a single agent and in combination with chemotherapeutic agents. Several Phase I and II clinical trials have been conducted to date in patients with solid tumor and hematologic malignancies; belinostat has been generally well tolerated.
- Belinostat is metabolized in the liver and therefore, the safety and dosing of belinostat needs to be established in patients with varying degrees of hepatic dysfunction.
- Establish the safety and tolerability of belinostat given on days 1 5 of 21-day cycles to patients with varying degrees of liver dysfunction.
- Define the maximum tolerated dose (MTD) and recommended dose of belinostat given on days 1 5 of 21-day cycles to patients with varying degrees of liver dysfunction.
- Evaluate the pharmacokinetics (PK) of one dose of belinostat (400 mg/m(2)) in patients with varying degrees of liver dysfunction.
- Obtain preliminary evidence of anti-tumor activity at tolerable doses of belinostat in patients with varying degrees of liver dysfunction.
- Determine polymorphisms in the UGT1A1 28 allele and correlate these with the observed toxicities and the PK of belinostat in patients with varying degrees of liver dysfunction.
- Measure direct versus indirect bilirubin levels and correlate these with observed toxicities, PK.
-Adults with solid tumors or lymphomas whose disease has progressed after standard therapy or who have no acceptable standard treatment options. Patients with normal and varying degrees of hepatic dysfunction (mild, moderate, and severe) are eligible.
-Patients will be divided into 4 cohorts based on their level of liver dysfunction. Belinostat will be administered IV over 30 minutes. On day -7 (Cycle 1 only), all patients will receive a single dose of 400 mg/m(2) belinostat. On days 1 5 of each cycle, patients will receive belinostat at a dose dependent on the level of hepatic dysfunction (see below). The total length of Cycle 1 will be 28 days; all other cycles will be 21 days. No more than 12 patients with normal hepatic function will be accrued.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01273155
|Contact: Deborah E Allen, R.N.||(301) firstname.lastname@example.org|
|Contact: Shivaani Kummar, M.D.||(301) email@example.com|
|United States, California|
|University of California, Davis||Recruiting|
|Davis, California, United States, 95616|
|City of Hope National Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|USC Norris Cancer Center||Recruiting|
|Los Angeles, California, United States|
|Contact: Shivaani Kummar, M.D. 301-435-5402 firstname.lastname@example.org|
|United States, Florida|
|Moffitt Cancer Center||Recruiting|
|Tampa, Florida, United States, 33647|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322-1102|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Shivaani Kummar, M.D. 301-496-4916 email@example.com|
|United States, Michigan|
|Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|United States, New York|
|Albert Einstein College of Medicine||Recruiting|
|Bronx, New York, United States, 10461|
|United States, Ohio|
|Case Western Reserve University||Recruiting|
|Cleveland, Ohio, United States, 44106-2602|
|United States, Pennsylvania|
|Penn State Hershey Cancer Institute||Recruiting|
|Hershey, Pennsylvania, United States|
|Pittsburgh Clinical Research||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15215|
|United States, Texas|
|Institute for Drug Development||Recruiting|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|